iOnctura SA, a clinical-stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface, has preclinical data that
shows its autotaxin inhibitor IOA-289 both inhibits pancreatic cells directly and inhibits the cancerpromoting activity of secreted factors from Cancer-Associated Fibroblasts (CAFS). The data will be shared via a poster (#2636) at the annual meeting of the American Association for Cancer Research (AACR) taking place on April 8-13, 2022 in New Orleans, Louisiana.
Autotaxin (ATX) is a secreted glycoprotein that hydrolyzes Lysophosphatidylcholine (LPC) to Lysophosphatidic Acid (LPA). LPA is a tumor cell growth activator and survival promotor. The AACR presentation demonstrates that by preventing LPA production, IOA-289 has a direct effect on pancreatic cancer cell lines (PDAC cells), inhibiting their growth in vitro.
LPA also modulates the tumor stroma which enables tumors to evade host immunity and impairs patients’ responses to therapy. Cancer Associated Fibroblasts (CAFs) are particularly important drivers of this effect and are responsible for supporting and promoting the growth of cancer cells via the secretion of soluble
mediators such as lipids (eg LPC) and cytokines. iOnctura’s data shows that addition of IOA-289 to CAF cultures inhibits the ability of these secreted factors to promote cancer cell growth in vitro. Further experiments with activated fibroblasts show that IOA-289 inhibits IL-6 and PAI-1 secretion, and likely contributes to the in vivo anti-tumorigenic nature of IOA-289.
These results provide further evidence for the mode of action of IOA-289 which acts directly on tumor cells and also modulates the immunosuppressive fibrotic microenvironment. IOA-289 represents a novel therapeutic strategy for the treatment of highly fibrotic, immunosuppressive (“cold”) cancer indications
such as pancreatic cancer that are resistant to therapy. A Phase I clinical study of IOA-289 in pancreatic cancer is in planning.
The poster presentation (#2636) at AACR is entitled “Targeting Autotaxin to Suppress Stromal Signaling in the Tumor Microenvironment to Improve Outcome to Therapy in Fibrotic Tumor Types.” The poster will be presented on Tuesday Apr 12, 2022 between 9:00 AM and 12:30 PM in New Orleans Convention
Center, Exhibit Halls D-H, Poster Section 24. The abstract is available in the AACR Online Proceedings planner and will also be published in the online supplement to the AACR journal Cancer Research approximately eight weeks after the AACR annual meeting.
The e-poster presentation will be available on iOnctura’s website following the meeting.